The long-term objective of the basic and clinical research program entitled "Proteins in Multiple Myeloma and Related Blood Diseases" has been to gain new insight into the pathogenesis of the human monoclonal light chain-related renal and systemic disorders and to 'develop more effective means to diagnose and treat individuals affected by these illnesses. Particular emphasis has been placed on primary (AL) amyloidosis - a monoclonal plasma cell dyscrasia associated with the production of amyloidogenic Ig light chains that form fibrillar deposits in vital tissues; this relentless process leads to organ failure and death within 9 to 36 months. Based on programmatic accomplishments, a highly focused, multidisciplinary experimental plan has been formulated to translate discoveries made during previous years of support into clinical practice. The specific aims include: 1) determination of the chemical nature of amyloid using microtechnology, including laser capture microdissection (Molecular Diagnosis of Amyloidosis); 2) visualization of amyloid by radiolabeled anti-fibril mAbs (Radloimaging of Amyloidosis); and 3) utilization of fibril-reactive mAbs to eliminate amyloid (Immunotherapy of Amyloidosis). These studies are designed to facilitate diagnosis, provide an objective means to detect and monitor systemic pathologic deposits, and utilize passive immunotherapy as a novel therapeutic modality. The ultimate goal is to improve the prognoses of patients with primary (AL) amyloidosis, a medically devastating and ultimately fatal disease.